Lactobacillus pentosus Alleviates Lipopolysaccharide-Induced Neuronal Pyroptosis via Promoting BIRC3-Mediated Inactivation of NLRC4

OBJECTIVE: Neurodegenerative disease is a common neurodegenerative disorder. Lactobacillus pentosus (L. pentosus) plays a neuron-protective role. This study aimed to investigate the effects of L. pentosus on neurodegenerative diseases. METHODS: Cells were treated with lipopolysaccharide (LPS) to establish neurodegenerative diseases model in vivo and with L. pentosus strain S-PT84. Reverse transcription-quantitative PCR (RT-qPCR) was applied to determine mRNA levels. Western blot was performed to detect protein expression. Cellular behaviors were detected using Cell Counting Kit-8 (CCK-8), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The interaction between baculoviral IAP repeat containing 3 (BIRC3) and NLR family CARD domain containing 4 (NLRC4) was predicted by STING and verified by western blot. RESULT: L. pentosus suppressed LPS-induced pyroptosis and promoted the cell viability of neurons. Additionally, L. pentosus suppressed the release of proinflammatory cytokines (interleukin 1 beta (IL-1β) and IL-18) and the protein expression of pyroptosis biomarkers (cleaved caspase1 (CL-CASP1) and N-terminal fragment gasdermin D (GSDMD-N)). Moreover, L. pentosus upregulated BIRC3, which induced the inactivation of NLRC4. However, BIRC3 knockdown alleviated the effects of L. pentosus and induced neuronal degeneration. CONCLUSION: L. pentosus may play a neuron-protective role via regulating BIRC3/NLRC4 signaling pathways. Therefore, L. pentosus may be a promising strategy for neurodegenerative diseases.